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Biomedical subjects

C Manuel

Publications and source records attributed to C Manuel.

At least 55 records · Page 3Linked to original sources
PubMed1987

Behavioural and biochemical studies on 6-methylamino-4,5,6,7-tetrahydrobenzothiazole (14.839JL), a new potent dopaminergic agonist.

6-Methylamino-4,5,6,7-tetrahydrobenzothiazole monochlorhydrate (14.839JL) is a new, potent dopaminergic agonist. The stereotypy induced by this drug was greater than that induced by an equivalent dose of apomorphine, was antagonized by pretreatment with sulpiride and counteracted the hypomotility induced by reserpine. Striatal levels of the dopamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were significantly lowered for up to 4-6 h by doses from 0.05 to 1 mg/kg. The drug was also very effective in lowering prolactine secretion. 14.839JL displaced [3H]N-n-propylnorapomorphine [3H]NPA from striatal binding sites with an IC50 similar to dopamine (DA). Conversely, the ability of 14.839JL to displace 3H spiperone from its binding sites was 100 and 10 times lower than that of haloperidol and sulpiride, and similar to that of SCH 23390. Differently from the latter, however, 14.839JL did not modify adenylate cyclase activity. All these data suggest that 14.839JL is a new, potent, long-lasting direct DA agonist, probably acting on D2 receptors.

Adenylyl Cyclases↗
PubMed1987

Pulmonary disposition of roxithromycin (RU 28965), a new macrolide antibiotic.

The penetration of roxithromycin (RU 28965), an ether oxime derivative of erythromycin, into the cells and fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiber-optic bronchoscopy with bronchoalveolar lavage on eight patients who had received roxithromycin at 300 mg perorally every 12 h for 5 days. The apparent volume of epithelial lining fluid recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. There was a significant relationship (r = 0.75; P less than 0.02) between roxithromycin levels in plasma and epithelial lining fluid, with a correlation whose slope suggested that the level of drug penetration into the lining fluid was 0.2. Concentrations of the antibiotic in cells recovered by bronchoalveolar lavage (21 +/- 10 micrograms/ml) were 2 and 10 times higher than in plasma (11.4 +/- 5.7 micrograms/ml) and epithelial lining fluid (2.0 +/- 1.7 micrograms/ml), respectively. Thus, when administered perorally in humans, roxithromycin is markedly accumulated by resident alveolar macrophages in concentrations largely exceeding the MBCs of the drug for most facultative intracellular pathogens including Legionella pneumophila, despite low concentrations in the epithelial lining fluid.

Bronchitis↗
PubMed1986

Short-term prophylactic antibiotics in patients undergoing prostatectomy: report of a double-blind randomized trial with 2 intravenous doses of cefotaxime.

The effect of short-term antibiotic prophylaxis on postoperative infection with 2 injections of cefotaxime begun preoperatively was evaluated in a double-blind, randomized, placebo-controlled trial at 1 center on 181 patients with preoperative sterile urine undergoing transurethral resection (90) or open prostatectomy (91). Antibiotic prophylaxis reduced the number of urinary infections significantly in both groups without altering the level of resistant pathogens. Cefotaxime lowered the incidence of postoperative infection in the early postoperative period from 30 to 4 per cent in the transurethral resection group and from 46 to 4.5 per cent in the open prostatectomy group. A significant difference was found between the 2 treatment groups in the incidence of perioperative bacteremia and postoperative fever. Among the patients undergoing an open prostatectomy a reduced rate of wound infection and a shorter duration of hospital stay were witnessed in the treated group. Thus, short-term chemoprophylaxis by cefotaxime is of benefit in reducing morbidity and hospital cost for prostatectomy by either procedure.

Cefotaxime↗
PubMed1986

[Indications and results of surgery in native valve infectious endocarditis. Apropos of 104 surgically-treated cases].

From 1972 to 1984, 104 cases of aortic valve infectious endocarditis were treated surgically. The average age of the patients was 40 years and the majority were men (69/104). Forty patients had no previous cardiac disease; 44 patients had documented valvular heart disease, which was unlikely in the remaining 20 patients. There were 16 mitral valve, 55 aortic valve, 1 tricuspid, 30 mitro-aortic, 1 mitro-tricuspid and 1 mitro-aorto-tricuspid valve infections. Aerococcus viridans was isolated in only 4 out of 71 positive cultures: the prevalence of the infecting organisms was otherwise normal (30 staphylococcus, 30 streptococcus, 7 rare organisms). Forty one patients were operated because of haemodynamic deterioration, 13 for resistant infection and 13 for an association of both indications; 37 patients were operated for embolism or threatening vegetations. Eight patients were in functional Class I, 26 in Class II, 52 in Class III and 17 in Class IV. The patients were divided into 4 groups according to the degree of surgical emergency (26 extremely urgent, 26 semi urgent, 32 controlled endocarditis and 20 chronic endocarditis). The actuarial survival rate was 70% at 5 years. Poor prognostic factors were the presence of previous valve disease, the isolation of a staphylococcus and an aortic valve localisation. The degree of emergency and the precise surgical indication did not seem to be important. Most patients at long term were in functional Classes I or II. There was no preferential indication for bioprosthetic or mechanical valve replacement in endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

[Evaluation of the posology of antibiotics].

The determination of the dose regimen of a new antibiotic is difficult because a dose/effect relationship cannot be established in patients with an infectious disease. The optimal dose is usually extrapolated from combined data provided by in vitro and in vivo microbiologic toxicologic and kinetic studies. Additional data ought to be produced in the future such as: kinetics of cidal effect in vitro, of the post antibiotic effect, of drug concentrations at the sit of infections itself, of the cidal serum activity in volunteers and patients; how these parameters are modified when modulating the mode of administration of the drug ought to be studied as well. The optimal dose, once it is roughly evaluated from classical studies, has to be adjusted: either by decreasing the dose, through an appropriate program of clinical trials with non-threatening life infections; or by increasing the dose in severe infections, through an in-depth analysis of new data available because of the improvement of: the design of clinical trials, the sensitivity of analytical techniques, the standardized serum bactericidal tests, the sophisticated monoparametric animal models simulating human infections, our knowledge of drugs mechanisms of toxicity. Establishing a rational dose regimen obviously requires a long-term multidisciplinary approach of the problem.

Animals↗
PubMed1985

[Effect of flash chemoprophylaxis by cefotaxime on the appearance of postoperative bacterial superinfections in surgery of the prostate].

The effect on bacteriologically documented postoperative infection of flash prophylaxis using two intravenous injections of 20 mg/kg cefotaxime each was evaluated in a double blind, randomized trial against placebo. 181 participants free of urinary tract infection prior to surgery had either transurethral prostatic resection (TUR) (n = 90) or open prostatectomy (OP) (n = 91). Urine samples, blood samples, prostate specimens and skin swabs were investigated for pathogens. Rate of urinary tract infection was significantly reduced by cefotaxime (CTX) prophylaxis in both groups. CTX lowered the incidence of early postoperative urinary tract infection from 30% to 4% in TURs and from 46% to 4.5% in OPs. Similarly, a significant difference was demonstrated for incidences of intra and postoperative bacteremia. In open prostatectomy patients, a reduced rate of wound infection and shorter hospital stay were noted in the treated group. Pathogens recovered in this study were Streptococcus (29%), Staphylococcus (20.5%), Enterobacteriaceae (45.75%), Pseudomonas (1.25%), Acinetobacter (3%), and Bacteroides fragilis (0.5%). CTX prophylaxis apparently has no bearing on postoperative emergence of resistant pathogens. Percentage of resistance to CTX in delayed postoperative infections was 33% in the control group and 35% in the treated group. We conclude that flash CTX prophylaxis in transurethral or open prostatectomy is of benefit in reducing morbidity and hospital costs.

Bacterial Infections↗
PubMed1985

[RU 28965, a new semi-synthetic macrolide. Bioavailability and pharmacokinetic profile after oral administration].

The plasma concentration of RU 28965, a new semisynthetic macrolide, was monitored for 24 h after single 400 mg oral doses in 8 healthy volunteers. Four tablet formulations were compared in a 4 X 4 latin square design, to assess the influence of micronization and enteric coating on bioavailability. Plasma samples were assayed for unchanged RU 28965 using HPLC. Extent of absorption was equivalent for all four formulations. Micronization did not significantly affect absorption characteristics, while enteric coating resulted in slower absorption. In the second part of the study, plasma concentration was monitored for 72 h after a single oral dose of two 150 mg non-coated, non-micronized tablets in another group of 12 subjects. The following pharmacokinetic parameters were found (m +/- sem) : cmax = 11.8 +/- 0.3 microgram.ml-1, AUC = 132 +/- 17 microgram.ml-1.h, t 1/2 = 12 +/- 0.5 h.

Absorption↗
PubMed1983

Ethacrynic acid facilitates gentamicin entry into endolymph of the rat.

Influence of ethacrynic acid (EA) upon gentamicin kinetics in perilymph and endolymph was studied in rats that were given a constant-infusion of gentamicin (150 micrograms/min) and EA (140 micrograms/min). Inner ear fluids and plasma were sampled up to 5 h. The purity of the endolymph was ensured by measurement of sodium and potassium concentrations. Gentamicin assay was done with a modified radioimmunoassay. Results show that EA facilitates the entry of gentamicin into endolymph, while it does not affect the kinetics of the drug in perilymph. Although the mechanism of this facilitation remains unclear, this result may account for the ototoxic potentiation reported between EA and aminoglycoside antibiotics.

Animals↗
PubMed1983

Gentamicin persistence in rat endolymph and perilymph after a two-day constant infusion.

The kinetics of gentamicin in the inner ear fluids of rats were studied up to 15 days after cessation of a 2-day constant infusion of 10 micrograms/min. In endolymph, the concentration of gentamicin persisted at about 1 microgram/ml for up to 15 days, precluding the determination of the half-life of the drug in this fluid. In perilymph, gentamicin cleared more slowly than after a shorter period of infusion. These results suggest that the tissues of the inner ear could bind the aminoglycoside and then slowly release it into the surrounding fluids.

Animals↗
PubMed1982

Moxalactam penetration into cerebrospinal fluid in patients with bacterial meningitis.

Penetration of moxalactam into the cerebrospinal fluid was studied in 11 patients with bacterial meningitis undergoing treatment with other antibiotics. Moxalactam at a dose of 20 mg/kg was administered as three 30- to 45- min infusions at 8-h intervals, once between days 2 and 4 and a second time between days 11 and 20 of treatment with the other antibiotics. Serum and cerebrospinal fluid were sampled 60, 90, or 120 min after the third moxalactam dose for measurement of the concentration of this drug by high-performance liquid chromatography. The concentration of moxalactam in cerebrospinal fluid ranged from 1.5 to 11 micrograms/ml, depending on the sampling time and the time elapsed since the onset of the disease. These concentrations in cerebrospinal fluid were equal to or higher than the minimum inhibitor concentrations for Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), and most of the gram-negative bacilli except for Pseudomonas aeruginosa. These results show that moxalactam has good penetrability when the meninges are inflamed and that it might be considered in cases of bacterial meningitis when the susceptibility of the pathogen indicates its usefulness.

Adult↗
PubMed1981

[Pharmacokinetic study of flubendazole in human hydatid disease caused by Echinococcus granulosus. Preliminary results (author's transl)].

A pharmacokinetic study of flubendazole was carried out, using a radioimmunological method, in patients with hydatid disease about to undergo surgery; there was no evidence of drug penetration into the walls or contents of the cysts. Another study, carried out simultaneously in subjects without hydatid disease, showed very high concentrations of the drug in liver tissue and in bile. These results should not be taken as arguments against the effectiveness of flubendazole, but should encourage the setting up of further randomized pharmacokinetic studies.

Adult↗
PubMed1981

Pharmacokinetics of gentamicin in perilymph and endolymph of the rat as determined by radioimmunoassay.

The kinetics of gentamicin in the inner ear fluids of the rat were studied with a sensitive radioimmunoassay. Continuous infusion over a broad range (7.5--150 micrograms/min) was used to obtain equilibrium. The lowest rate of infusion produced plasma concentrations after 45 min that were within the range of peak serum levels desirable in humans. The purity of perilymph and endolymph was ensured by measurement of sodium and potassium concentrations. The concentration of gentamicin in perilymph was linearly related to its concentration in plasma, which depended on the rate of infusion. After six days of constant infusion of gentamicin at 15 microgram/min, the concentrations in plasma, perilymph, and endolymph averaged 25.8, 5.1, and 1.2 micrograms/ml, respectively, for five of 11 rats. Gentamicin cleared from the perilymph with a half-life of 3 hr.

Animals↗
PubMed1981

Radioimmunoassay of gentamicin in microliter and nanoliter samples of biological fluids.

A gentamicin radioimmunoassay is described for microliter and nanoliter samples. The assay was performed in the inner ears' fluids (perilymph and endolymph) of rats. Endolymph and perilymph samples were collected under oil with a glass capillary micropipette. The absolute threshold of sensitivity was 20 . 10(-12) g. Considering the maximum sampling volume, 15--400 . 10(-9) and 10 . 16(-6) l for endolymph and perilymph respectively, the limit of detection is 4.19 . 10(-4) microM . ml-1 in endolymph, 1.26 . 10(-4) microM . ml-1 in perilymph. Clinical applications of this method are suggested.

Animals↗